Term
| Of the adrenergic drug subtypes, what does direct and indirect acting mean? |
|
Definition
Direct - agonists & antagonists act DIRECTLY on the receptors to block/exaggerate response
Indirect - these effect the release of nt from the presynaptic cleft |
|
|
Term
| Name 5 catecholamines and what receptors they are specific for? |
|
Definition
Epinephrine (epi) - alpha1,2,beta1,2
NE - alpha1,2, beta 1 only
Isoproterenol (IPNE) - beta 1 and 2 only
Dopamine - beta 1, dopamine receptor 1 and 2 (D1 and D2)
Dobutamine - beta 1 only |
|
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Term
| All catecholamines are derivates of what? What do all catecholamines have that are differnt from this derivative? |
|
Definition
| Phenylethylamine + OH's on C3 and C4 of the benzene ring |
|
|
Term
| Is ephedrine a catecholamine? Why? So what are the consequences? |
|
Definition
NO, it lacks the 2 OH's on C3 and C4 of the beneze ring....therefore:
1. its less polar and can effect CNS more
2. it has a longer half life cuz MAO and COMT cannot degrade it |
|
|
Term
| Why can't catecholamine X BBB? |
|
Definition
| 2 hydroxy groups on its benzene ring |
|
|
Term
| For alpha receptors, rank how well the 3 catecholamine can bind (NE, Epi, IPNE) |
|
Definition
|
|
Term
| For betareceptors, rank how well the 3 catecholamine can bind (NE, Epi, IPNE) |
|
Definition
|
|
Term
| What does activation on a1 receptor do in the bladder's sphincter? |
|
Definition
| increase tone (increased closure) |
|
|
Term
| What does a2 receptor do when activated? |
|
Definition
Inhibits NE release, inhibits ACh releaes, inhibits insulin release, causes vasodilation post-synaptically
**first 3 are all from pre-synaptic cleft |
|
|
Term
| Besides heart stuff, what else can beta1 do to kidney and fat? |
|
Definition
kidney - increase renin release
fat - increase lipolysis |
|
|
Term
| Beta2 receptor activated. Name the effect on the BV's, BP, bronchus,liver,pancreas, uterine smooth muscle |
|
Definition
BV's - vasodilation
BP - slight drop in BP
bronchus - bronchodilation
liver - increased gluconeogenesis and glycogenolysis
pancreas - increased glucagon secretion
uterine smooth muscle - relaxation |
|
|
Term
| What kinds of receptors does NE like best and worst (relatively speaking) |
|
Definition
| alphas>beta1 (NO beta 2's) |
|
|
Term
| What kinds of receptors does EPI like best and worst (relatively speaking) |
|
Definition
beta2>bet1>alpha
beta2 = vasodilation
alpha = vasoconstriction, therefore
at low epi concentrations , SLIGHT vasodilation seen, but at HIGH EPI concentrations, vasoconstriction seen
**this is only seen in vascular beds with BOTH B2 and a1 receptors - like BV's supplying SKELETAL MUSCLES and CORONARY VESSELS |
|
|
Term
| What receptors are found on cutaneous vasular beds? What about skeletal muscle vascular beds? What is the consequence? |
|
Definition
cutaneous - only alpha's
skeletal muscle - B2 and alphas
Therefore, when Epi is around in low doses it will cause vasodilation (cuz epi has more affinity toward beta2's), but when epi is around in high doses, vasoconstriction (alpha caused vasoconstriction may more powerful then beta2's vasodilation. alpha1's response wins = vasoconstriction) |
|
|
Term
| Drugs that activate _____ receptors better (like NE) on the vasculature elicit a stronger baroreceptor response (bradycardia |
|
Definition
|
|
Term
| Who will elicit a stronger baroreceptor reflex? Epi or NE? Why? |
|
Definition
| NE....NE acts on alpha receptors first whereas EPI acts on B2, then B1 and finally alpha's if concentrations get high enough |
|
|
Term
| Blood pressure effects of EPI, NE, IPNE are a combination of what? |
|
Definition
| Peripheral resistance effects (a1 or b2?'s) + Pulse rate of heart (determined by B1 response & reflex response from periph. resistance) |
|
|
Term
| When is EPI used in clinic? |
|
Definition
Emergencies:
cardiac resuscitation (b1)
relief from anaphylaxis (b2)
bronchospasm (b2)
Reduce IOP in OPEN ANGLE glaucoma (a1)
Adjunct to anesthesia - prolonged duration (a1)
topical hemostatic agent (a1) |
|
|
Term
| What is the duration of action of epi and why? |
|
Definition
| Very short....MAO and COMT quickly degrade...they are in the liver and gut |
|
|
Term
| What is the onset of EPI? |
|
Definition
| VERY QUICK....why its used in emergenices...very high affinity & potency to adrenergic receptors |
|
|
Term
| Why can we not give epi orally? |
|
Definition
|
|
Term
| What are some the side effects of EPI related to blood sugar? |
|
Definition
| Hyperglycemia...when it binds b2 increases g&g of liver + glucagon secretion from pancreas |
|
|
Term
| What are the heart's side effects to epi? |
|
Definition
Direct tachycardia
Reflexive bradycarida (huge increase in BP causes baroreceptor reflex to tell the heart to "Slow down!" |
|
|
Term
| Hyperthyroidsm + EPI. Consequences? |
|
Definition
| Hyperthyroidism supersensitizes the adrenergic receptors apparently, so CARDIOVACULAR effects are much greater |
|
|
Term
| Diabetes + EPI. Consequences? |
|
Definition
| EPI increases BP...so diabetic might have to increase their insulin |
|
|
Term
| Beta-blockers + EPI. Consequences? |
|
Definition
| Increased alpha response (cuz epi has nowhere else to go besides alphas cuz betas are blocked)...increase in BP! |
|
|
Term
| What is NE pretty much used for? |
|
Definition
| Rarely...but reverse hypotensive shock (cuz it ignores B2's and gets a1's and b1's!) |
|
|
Term
| What is Isoproterenol used for? |
|
Definition
| Nothing....replaced by albuterol |
|
|
Term
| What is the immediate precursor to NE and EPI? |
|
Definition
|
|
Term
| What is dopamine's relationship with the kidneys? |
|
Definition
| epithelial cells of the proximal tubule secretes it as a local diuretic and natiuretic. D1 receptors on the loop of Henle and Ascending thick limb bind dopamine. This inhibits Na pumps --> more fluid excreted |
|
|
Term
| Where are D2 receptors? What can bind them? What are the effects? |
|
Definition
| Found only in presynaptic adrenergic neurons. ONLY dopamine can bind. This will INHIBIT NE release |
|
|
Term
| What can VERY HIGH doses of dopamine do? |
|
Definition
|
|
Term
| What are the clinical uses of dopamine? |
|
Definition
Improve cardiac and renal function in critially ill people with heart failure + renal failure
Cardiogenic and Septic shock |
|
|
Term
| When using dopamine to treat shock, what must we accompany with it? |
|
Definition
| Fluids...they are already hypovolemic and a diuretic would just make it worse |
|
|
Term
| What will dobutamine bind? |
|
Definition
| B1 only....its - and + enantiomers are agonists and antagonists of alpha1's, respectively, so that interaction nets a cancel out |
|
|
Term
| Dobutamine has more ____tropic effects on the heart than ____tropic. |
|
Definition
iono-
chron- (those that change the heart rate) |
|
|
Term
| What is the clinical use of dobutamine? |
|
Definition
| Short-term cardiac decompensation after surgery, MI, or CHF....increases CO and SV WITHOUT much HR or BP increase |
|
|
Term
| Name a nonselective alpha agonist. What is it used for? |
|
Definition
| Oxymetazoline...nasal decongestant |
|
|
Term
| What will happen if someone uses too much oxymetazoline? |
|
Definition
Nonspecific alpha agonist...nasal decongestant
At first...desensitization of a1 receptors in nose. This will make the problem EVEN WORSE than before. Next when its not working, patient will take EVEN MORE, causing so much vasoconstriction that it nasal tissue will die (just like any tissue that loses its O2 supply) |
|
|
Term
| What is an alpha1 selective agonist? What would it be used for? |
|
Definition
| Phenylephrine...nasal decongestant and mydriatic agent |
|
|
Term
| Phenylephrine vs. oxymetazoline for nasal decongestant? |
|
Definition
| phenylephrine....less damaging |
|
|
Term
| What is the advantage of using phenylephrine (a1 agonist) over atropine (anticholinergic) |
|
Definition
| phenylephrine doesn't mess with accomodation. atropine might cause loss of accomodation |
|
|
Term
| When is phenylephrine contraindicated in glaucoma? |
|
Definition
| During narrow/closed angle glaucoma. phenylephrine will dilate pupil...iris will bundle up and block humor flow |
|
|
Term
| When can phenylephrine be used in emergencies? Advantages over EPI? |
|
Definition
Short-term hypotensive emergencies
Less potent but LONGER DURATION than EPI (not a catecholamine, therefore not broken down by COMT) |
|
|
Term
|
Definition
1. Treat hypertension
2. Withdrawl from drugs |
|
|
Term
| What does clonidine target? |
|
Definition
| selective alpha2 PARTIAL agonist |
|
|
Term
| What is a partial a2 agonist? |
|
Definition
|
|
Term
| Since clonidine is a partial a2 agonist, how come it LOWERS BP??? |
|
Definition
| It easily X's BBB and gets into CNS. In CNS, it targets lower brainstem to DECREASE SYMPATHETIC OUTFLOW to heart and vasculature |
|
|
Term
| When going thru a withdrawl, your __NS has increased activity, which is why we use _____ to treat this. |
|
Definition
| Sympathetics are increased during withdrawls. Clonidine decreases this....its a presynaptic alpha 2 partial agonist. It will inhibit NE release |
|
|
Term
| Clonidine, if given IV, will cause transient ____tension followed by prolonged ____tension |
|
Definition
|
|
Term
| What are some side-effects of clonidine? |
|
Definition
Dry mouth, SEDATION, bradycardia, sexual dysfunction
Many get these symptoms but most "grow out" of them in a few weeks....if they don't grow out, discontinue drug use. |
|
|
Term
| Abrupt discontinuation of chonidine. Good idea? Consequences? |
|
Definition
| Rebound hypertension (from a rebound sympathetic increase) |
|
|
Term
| What is apraclonidine used for? Why is it better than other? |
|
Definition
Selective a2 agonist
Used topically to reduce IOP
Less likely to cause mydriasis (cuz it doesn't mess with a2) |
|
|
Term
| Name 2 beta1 selective agonist drugs. |
|
Definition
dopamine (also goes for D1 and D2 also)
Dobutamine |
|
|
Term
| name 3 bet2 selective agonists |
|
Definition
| albuterol, salmeterol, ritodrine |
|
|
Term
| Onset and duration of action for albuterol vs. salmeterol |
|
Definition
Albuterol: 15 mins (onset) 2-3 hour (duration)
Salmeterol: 1 hour, 12 hours |
|
|
Term
| What is better for COPD: salmeterol or albuterol? |
|
Definition
|
|
Term
| Which has A LITTLE anti-inflammatory property: salmeterol or albuterol? |
|
Definition
|
|
Term
| What do we need to know about ritodrine? |
|
Definition
| Beta2 agonist. Relaxes uterine muscle when given IVly to delay premature labor |
|
|
Term
| What are some side effects of b2 agonists? |
|
Definition
Increased HR (b1)
Tremor (b2) - effects skeletal muscle
Decreased plasma K+ concentration (b2)...causes skeletal muscle to uptake K+
Increased plasma glucose (b2) (it says b2 increases liver g&g but it also says that it increases insulin secretion but another slide also says that b2 activation increases glucagon secretion???) |
|
|
Term
| Name 2 non-selective alpha antagonists |
|
Definition
Phenoxybenzamine (we talk about this one more &
Phentolamine - "just remember this one's name" |
|
|
Term
| Treating Phenochromocytoma...what do we use? |
|
Definition
| Phenoxybenzamine...its a nonselctive alpha antagonist. This is a carcinoma of the adrenal medualla which pumps out tons of EPI...so phenoxybenzamine counterbacts it by blocking alphas |
|
|
Term
| What is the MOA for phenoxybenzamine? |
|
Definition
| IRREVERSIBLE antagonist of both alpha receptors...decreases peripheral resistance and preload |
|
|
Term
| What the MOA for prazosin? |
|
Definition
| a1 antagonist...decreases peripheral resistance and preload by ACTING IN THE CNS!!! |
|
|
Term
| What are the benefits of prazosin over phenoxybenzamine? |
|
Definition
Prazosin will give LESS REFLEXIVE tachycardia
Phenoxybenzamine goes after a2 and a1. since it also goes after a2, its will stop its inhibition of NE release at presynaptic ganglia, allowing more NE release. Therefore phenoxybenzamine will result in DIRECT TACHYCARDIA, whereas prazosin will will have NOTHING to do with direct tachycardia cuz prazosine is ONLY a a1 antagonist |
|
|
Term
| Phenoxybenzamine and prazosin: which one X's BBB? |
|
Definition
| Prazosin....cuz it goes there and suppresses sympathetic outflow |
|
|
Term
| Clinical use of Prazosin? |
|
Definition
| Treat hypertension, CHF, and BPH |
|
|
Term
| What do we usually adjunct with prazosin and why? |
|
Definition
| Prazosin causes water/Na retension, therefore we add a diuretic |
|
|
Term
| How do we dose prazosin thru the day and why? |
|
Definition
| It causes marked hypotension in the first 30-90 mins of its FIRST USE (of the day). We give less in the first dose and increase doses thru the day |
|
|
Term
| What is tamsulosin used for? |
|
Definition
|
|
Term
| What receptor does tamsulosin target? |
|
Definition
| alpha1's of the PROSTATE! THis decreases the increased tone seen in BPH of the prostate and the trigone, and the internal urethral sphincter |
|
|
Term
| Why is tamsulosin better than prazosin to treat BPH? |
|
Definition
| Tamsulosin acts ONLY at the a1's of the prostate/trigone/urethral sphincter to treat BPH...whereas prazosin will affect all a1's |
|
|
Term
| What are 3 first generation beta antagonists....and what does 1st generation mean? |
|
Definition
First generation is non-selective beta antagonists
Propranolol, timolol, sotalol |
|
|
Term
|
Definition
|
|
Term
| What are 3 2nd generation beta antagonists and what does 2nd generation mean? |
|
Definition
2nd generation is B1 specific
atenolol (tenormin)
esmolol
metoprolol |
|
|
Term
| Name 3 third generation beta antagonists and what does third generation mean? |
|
Definition
Third generation means they have "additional protective benefits"?
Non-selective 3rd gen.:Labetalol and carvedilol'
b1 selective 3rd gen.:nebivolol |
|
|
Term
| Most beta blockers _____ get into the CNS. Side effects? Which ones? |
|
Definition
| DO NOT! but propanolol, timolol, and metoprolol do...they cause lethargy, depression, and confusion |
|
|
Term
| What do beta blockers do to membrane potential? |
|
Definition
| They hyperpolarize (stabilize) membranes by blocking Ca entry and opening K channels |
|
|
Term
| Why would beta blockers help prevent migrane? |
|
Definition
| Migraines have vasodilated cerebral vessels...so if beta blockers stop the dilation it can be an effective PROPHYLACTIC treatment |
|
|
Term
| How can propanolol treat thyrotoxicosis? |
|
Definition
| it reduces HR (like all beta blockers) but it also inhibts 5 deiodinase, which is responsible for converting T4 to T3 in tissues |
|
|
Term
| What does propanolol do to renin? |
|
Definition
|
|
Term
| What is Timolol and what is it used for? |
|
Definition
| non-selective beta blocker (1st gen) used to treat glaucoma by decreasing aqueous humor production |
|
|
Term
| Why do we use atenolol in some patients as a beta blocker? |
|
Definition
| Atenolol is a 2nd generation beta blocker and only goes after beta1's. The sparing of beta2's indicates its use in ASTHMATICS |
|
|
Term
| What's the main difference of symptoms between 1st/2nd generation beta blockers and 3rd generation? |
|
Definition
| 1st and 2nd generation can mask the symptoms of hypoglycemia. Diabetic know how to feel if their blood sugar is slow by feeling an increase in sympathetic acitvity. 1st and second gen. beta blocker are good at decreasing this sympathetic activty thru out the body. 3rd generations are better at doing what they are intended to do without masking the symptoms by not decreasing the sympathetic activity too much so the diabetic can still tell when they need sugar |
|
|
Term
| What receptors do 3rd generation beta blockers affect? |
|
Definition
BETA 2 AGONIST!!!
ALPHA 1 ANTAGONIST
beta 1 antagonist |
|
|
Term
| What is labetolol and what is it used for? |
|
Definition
3rd generation nonselective beta1 blocker
Used for hypertensive emergencies |
|
|
Term
| What is MOA of labetolol? |
|
Definition
Its a 3rd generation non-selective beta blocker
increases cardiac contractility, and rate (b1 blocking)
decreases peripheral resistance (b2 agonist AND alpha1 antagonist) |
|
|
Term
| What is carvediol and what is it used for? |
|
Definition
| non-specific third generation beta-blocker used for hypertension & moderate-severe CHF |
|
|
Term
| What is the MOA for carvedilol? |
|
Definition
increases HR and contractility (b1)
decreases peripheral resistance (alpha1 blocking)
Its also a free radical scavanger
Improves insulin sensitivity compared to Metoprolol |
|
|
Term
| What is better for insulin sensistivity: metoprolol or carvedilol? |
|
Definition
| Carvediolol - it a 3rd generation beta blocker. metaprolol is a 2nd generation (beta1 specific) |
|
|
Term
| What is nebivolol and what is it used to treat? |
|
Definition
| 3rd gen. beta blocker....tx of hypertension |
|
|
Term
| What is the MOA os nebivolol? |
|
Definition
high b1 selectivity
reduces HR and contactility (b1)...so don't give to CHF pt.
antioxidant
increases bioavailibility of NO
reduces peripheral res. while maintaining cardiac output |
|
|
Term
| How do amphetamines work? |
|
Definition
Increase release of dopamine by:
inhibiting its uptake back into presynaptic cell (allowing to sit in terminal longer)
Inhibiting MAO
Inhibiting dopamine vesicular transporters???? |
|
|
Term
| What is a mixed acting sympathomimetic? What receptors does it work at? |
|
Definition
| ephedrine....ALL adrenergic receptors (direct) AND increases DA and NE release (indirect, therefore mixed acting) |
|
|
Term
| Name 2 indirect acting sympahtolytics and what we are supposed to know about them. |
|
Definition
methyl-tyrosine (metryosine) - inhibits tyrosine hydroxylase
Methyldopa (aldomet) - makes a false nt called methyl-NE. Used to treat hypertension in pregnancy |
|
|
Term
| Name 2 non-specific MAO inhibitors |
|
Definition
| Phenelzine, Tranylcypromine |
|
|
Term
| Name 1 specific MAO inhibitor |
|
Definition
|
|
Term
|
Definition
|
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